“These results show objective endpoints, subset selection, and recovery. There were complete responders and partial responders among severely ill CFS patients with HHV6 or CMV. These are encouraging results for this subset and further well-designed trials should be pursued to confirm them.” Dr. Dan Peterson

At the HHV6 Conference in Paris, France today Dr. Peterson reported on the results of a retrospective study following 65 severely ill chronic fatigue syndrome patients given a course of Vistide from 2005-2012 for HHV6 and/or HCMV infections. Despite the interest in pathogens in ME/CFS, antiviral studies are rare and this is the first one reported for this drug.

Vistide (Cidofovir) gets a lot less press than other antivirals and immunomodulators (Ampligen, Rituximab, Valcyte, Valtrex) used in this disorder probably because the drug requires a complex infusion protocol, frequent blood tests because of the rare but real possibility of serious kidney side effects and is expensive (although it can be covered by insurance).

This combination – infusions, frequent blood tests and expense – requires close physician follow-up. With Dr. Peterson’s specialized focus on patients with dysfunctional natural killer cells, however, he may be most consistent about testing for herpesviruses, which are known to be active in ME/CFS patients.

After three decades of focusing on immunologically challenged ME/CFS patients, Peterson may be more experienced at pathogen detection and treatment than any other practitioner in the field, and so it’s not surprising to find the first Vistide study coming from his office. In an interview, a former patient of his said, ‘he leaves no stones unturned’; when he finds something he goes after it ‘aggressively’.

In his presentation he stated almost 30% of his patients test positive for active HHV-6 or human cytomegalovirus (HCMV) (PCR, rapid culture, antigenemia), and a whopping 50% test positive for active Epstein-Barr virus (EBNA) infection.

Serious Drug For A Serious Illness

Vistide (Cidofovir) is FDA approved for the treatment of cytomegalovirus (CMV) in patients with AIDS. (Cytomegalovirus is a member of the herpesvirus family.) and it’s been used off-label to treat human papillomavirus, BHK virus, herpes simplex virus, vaccinia virus infections. The Black Box warning on Vistide speaks for itself

‘Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with few as one or two doses of Vistide. The “recommended dose, rate, frequency of Vistide injections must not be exceeded.”

The Study

A positive response was denoted by a negative pathogen test, improved fatigue and cognitive functioning determined by an interview with Dr. Peterson and the patient’s self reports after the trial.

Response

Full Responders – Patients were deemed to be full responders if they were able to completely return to work or to work-related activities

Partial Responders – demonstrated significant improvement of symptoms but were unable to return to work or work related activities.

Non-Responders – Did not demonstrate any measurable improvement post-treatment

Results

Dr. Peterson reported that seventy percent of patients were full (able to return to work) or partial (significant increase in functionality) responders; a very high rate of success in a illness characterized by a poor response to treatments. Only thirty percent of Vistide recipients did not have a significantly positive response to the drug. No serious side effects were seen; ironically the minor side effects seen were attributed to a drug, Probocenid, used to ensure Vistide was safe.

It’s not clear what percentage of ME/CFS patients will test positive for HHV6 or cytomegalovirus in other practices but this type of response suggests the drug may be being under-used. With the FDA Stakeholder’s meeting coming up in three weeks and the Chronic Fatigue Initiative’s pathogen discovery study results due to be published later this year, Dr. Peterson’s presentation is timely. (Unfortunately, Dr. Peterson was not invited to present at the FDA Stakeholder’s Meeting.)

Dr. Peterson called for placebo-controlled, double-blinded multi-center studies that address Vistide’s efficacy, examine its effects on the immune system and study the mechanisms of increase in VO2 max scores in ME/CFS.

Sample Cases

Dr. Peterson reported on several cases, all of whom were men – something Dr. Peterson has said he likes to do to break up the notion that only women get this disorder.

A 27 year old college graduate unable to work because of constant flu-like symptoms, weakness and marked cognitive decline (math!) presented with low NK functioning, low VO2 max and HHV6 and cytomegalovirus infection. He was able to return to work after 24 weeks of bi-weekly infusions. His VO2 max on the exercise test went up went up 23%, his NK cells a remarkable 400% and he tested negative for both viruses at the end of treatment. He had had ME/CFS for three years.

A 54 year-old former high school teacher unable to work due to extreme fatigue, flu-like symptoms and cognitive problems severe enough to keep him from being able to grade his students papers presented with active HHV6 and cytomegalovirus infections and low NK cell functioning and VO2 max. He was able to return to work after 24 weeks of bi-weekly infusions. His VO2 max increased 47%, his NK function test went up 20% and he tested negative for both viruses. He had had ME/CFS for five years.

The third patient had classic, acute onset ME/CFS which progressed to seizures. Both serum and cerebral spinal fluid tested positive for HHV6. At the end of the Cifodovir trial the viral load in his cerebral spinal fluid dropped from 3670 copies/ml to undetectable levels. Serum HHV6 was dramatically reduced (47,000 copies/ml to 3,000 copies/ml). Still symptomatic and experiencing cognitive problems, he was nonetheless able to return to work.

Conclusions

Increasing VO2 max appeared to be critical to increasing functionality as the partial responders did not increase their VO2 max while on Cifodovir. At the FDA Advisory Meeting for Ampligen Dr. Bateman noted that VO2 max test results probably were, given the exertional problems in ME/CFS, the most difficult to ‘move’ test result in this disorder.

VO2 max levels in Dr. Peterson’s patients prior to Vistide administration were exceedingly low; they appeared to in the ‘very low’ range even for people for 65 years of age and older. Vistide moved those test results about 20% on average; leaving them still, it appeared, below normal but sufficient enough for a significant increase in functionality.

A Vistide Example

The VO2 max tests suggested most patients had not returned to full health and Dr. Peterson has said he knows of few complete recoveries. I interviewed a former patient of Dr. Peterson’s several years ago. Faced with the loss of his career and the ability to care financially for his family Vistide turned out to be a godsend.

Cut down by acute onset ME/CFS, his VO2 max score topped out at an unbelievably low 15 (which qualified him for heart disease) and he was a ‘2’ out of 10 on his own energy scale (had trouble sitting up to eat). Within a month on Vistide he was at a ‘4’; the next month he was a ‘5’ and sleeping soundly for the first time since he’d gotten sick. The next month he was a ‘7’ and his VO2 max tests had doubled to 28; still far below the 44 expected at his age, but an amazing increase, never the less. Three months later he was at ‘90%’, back at work and able to do everything except exercise.

CMX001 – The Future Vistide?

Dr. Peterson didn’t report on CMX001 in Paris, but sitting in the background of all this is a analogue of Vistide called CMX001 which appears to be a safer and more effective, if not yet available, version of it. A 2012 review named CMX001 as one the ‘ten hot topics’ in antiviral research.

Chimerix Pharmaceuticals modified Vistide so that it can easily be taken up into the tissues. That means no need for infusions, no worries about kidney problem and according to Chimerix, dramatically increased effectiveness.

CMX001 has been in development for some time but just this March the FDA awarded the drug ‘fast track’ status for the prevention of cytomegalovirus infection. Phase II trials are finished and Phase III trials will get underway this year.

Given Dr. Peterson’s success with Vistide, FDA approval of CMX001 could be very good news for ME/CFS patients with HHV6, HCMV and/or possibly EBV infections.

Wrap Up

In a retrospective study Vistide proved to be effective in treating severely ill ME/CFS patients with HHV6 and HCMV infections. Dr. Peterson called for double-blinded, placebo-controlled studies to further study Vistide’s efficacy and mechanism of effect. The CFI’s pathogen discovery studies due out this year should shed light on what percentage of ME/CFS patients could benefit from Vistide.

A Vistide analogue under development called CMX001 which does not require infusions and does not effect the kidneys could be boon for ME/CFS patients with herpesvirus infections if it is approved by the FDA. CMX001 was given fast-track status by the FDA earlier this year.